How does TNF-alpha act, and can we target its down stream target CJSAN 2015

TNF-alpha signaling cascade includes JAK pathways. Inhibition of JAK pathway (JAK1, and JAK3 by Tofacitinib led to similar efficacy as Adalimumab in RA. Ofnote, significant side effects (sepsis, neutropenia, elevated Liver enzymes, elevated Cr) were seen as it probably also lacks specificity.